If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Threonine Degradation|
Microorganisms and mammals share two of the major, initial routes for threonine degradation. In the first route threonine is catabolized by catabolic threonine dehydratase (EC 188.8.131.52) to ammonia and 2-oxobutanoate. A biosynthetic version of this enzyme also occurs (see threonine deaminase) [Umbarger57]. In the second route threonine is catabolized by threonine dehydrogenase (EC 184.108.40.206) to form 2-amino-3-oxobutanoate, which is mainly cleaved by 2-amino-3-ketobutyrate CoA ligase, forming glycine and acetyl-CoA. The 2-amino-3-oxobutanoate can also be spontaneously converted to aminoacetone, which may be further metabolized to methylglyoxal (see threonine degradation III (to methylglyoxal)). A third route has been demonstrated in several bacteria and fungi. This route is based on the enzyme low-specificity L-threonine aldolase (EC 220.127.116.11), which cleaves threonine directly into glycine and acetaldehyde.
Escherichia. coli has been shown to assimilate nitrogen from some (but not all) amino acids, as well as agmatine, γ-aminobutyrate and the polyamines putrescine and spermidine. These nitrogen sources are used to generate glutamate and glutamine, the major intracellular nitrogen donors. Some nitrogen sources, such as aspartate, can generate glutamate by transamination (see aspartate aminotransferase, PLP-dependent). Others, such as proline and arginine, produce glutamate as end products (glutamate generating amino acids) (see proline degradation and arginine degradation II (AST pathway)). Other nitrogen sources, such as serine, require ammonia production for glutamate synthesis (ammonia generating amino acids) (see L-serine degradation). Ammonia generation is required for glutamine synthesis (see glutamine biosynthesis I).
In E. coli a low intracellular level of ammonia results in low intracellular glutamine and induction of the nitrogen-regulated (Ntr) response that involves response regulators NtrC transcriptional dual regulator and NtrB sensory histidine kinase. The Ntr response functions in ammonia assimilation, nitrogen scavenging and metabolic coordination.
E. coli has three systems that can transport threonine: serine / threonine:Na+ symporter [Kim02a], branched chain amino acid ABC transporter [Robbins73], and serine / threonine:H+ symporter TdcC [Sumantran90]. Although E. coli can use threonine, glycine, or serine as a nitrogen source, efficient serine or threonine utilization requires amino acid supplementation. Leucine supplementation is required for the use of threonine as a nitrogen source in pathways utilizing threonine dehydrogenase (TDH) which is induced by leucine [Potter77] (see threonine degradation II and threonine degradation III (to methylglyoxal)). TDH is is a major route for threonine degradation in E. coli. A minor pathway is shown in threonine degradation IV and an anaerobic pathway is shown in threonine degradation I.
About This Pathway
Enteric bacteria such as Escherichia coli K-12 and Salmonella enterica subsp. enterica serovar Typhimurium have been shown to possess two types of threonine dehydratases - a catabolic enzyme, which is induced by threonine (see catabolic threonine dehydratase), and a constitutively-produced biosynthetic enzyme (see threonine deaminase) [Umbarger57]. Both enzymes convert threonine to 2-oxobutanoate. While the biosynthetic enzyme is involved in isoleucine biosynthesis (see isoleucine biosynthesis I (from threonine)), the catabolic enzyme participates in the degradation of threonine to propionate in a pathway that generates ATP and enables the utilization of threonine as a sole source of carbon and energy [Luginbuhl74]. This E. coli anaerobic threonine dehydratase pathway is shown here [Sawers98, Hesslinger98].
The first reaction in this pathway is catalyzed by catabolic threonine dehydratase which degrades threonine to 2-oxobutanoate (α-ketobutyrate) and ammonia. The 2-oxobutanoate then undergoes lyase cleavage with the addition of coenzyme A to form propanoyl-CoA and formate. Two such lyases were discovered in E. coli K-12 [Hesslinger98]. Both of these enzymes, pyruvate formate-lyase / 2-ketobutyrate formate-lyase encoded by gene pflB and 2-ketobutyrate formate-lyase / pyruvate formate-lyase 4 encoded by gene tdcE, are expressed only under anaerobic conditions, and both utilize a glycyl radical as part of their catalytic mechanism [Sawers98b]. TdcE is equally active with 2-oxobutanoate and pyruvate substrates, whereas PflB prefers pyruvate. Once propanoyl-CoA is formed, it is processed via propionyl-phosphate to propionate in a reaction sequence that produces ATP. Acetate kinase AckA can also utilize propionate as a substrate in the final reaction. The enzymes in this pathway are also able to process L-serine, with pyruvate as the final product [Sawers98].
Features of this energy-generating pathway include substrate-level phosphorylation, a requirement for cAMP-CRP, and catabolite repression. The tdcABCDEFG operon genes also encode serine / threonine:H+ symporter TdcC (see above), L-serine deaminase III, and predicted enamine/imine deaminase. Regulators of the operon include adjacent TdcR DNA-binding transcriptional activator, CRP transcriptional dual regulator, IHF DNA-binding transcriptional dual regulator, and TdcA DNA-binding transcriptional activator. This pathway does not appear to be essential because inactivation of tdcB [Goss84]. tdcE [Hesslinger98], or tdcD [Hesslinger98] resulted in no discernible phenotype.
Superpathways: superpathway of threonine metabolism
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